Department of Anesthesiology, Shanghai Sixth Municipal Hospital, Shanghai Jiaotong University, China.
Acta Pharmacol Sin. 2012 Jan;33(1):27-33. doi: 10.1038/aps.2011.155. Epub 2011 Dec 12.
To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion.
Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24 and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting.
The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P.
Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.
探讨丙泊酚输注综合征（PRIS）的发病机制，PRIS 是长时间输注丙泊酚时可能致命的并发症。
通过气管插管进行机械通气的雄性兔分为 3 组（每组 6 只），分别用 1%丙泊酚（P 组）、异氟烷（I 组）或异氟烷同时接受 10%脂肪乳（II 组）镇静。在治疗开始后 0、6、12、18、24 和 30-36 h 采集血液生化参数。实验结束后立即取出心脏，用免疫组织化学法研究心脏中肿瘤坏死因子（TNF）-α的水平。用 Western blot 法评估心脏中 AMP 激活的蛋白激酶（AMPK）和磷酸化 AMPK。
P 组死亡率为 50%，I 组和 II 组均为 0%。P 组血清脂质和肝功能指标明显升高，而 II 组中度升高。I 组这些指标明显下降。所有组均显示肌酸激酶（CK）明显释放。P 组所有心脏样本均显示 TNF-α强阳性染色，而 II 组和 I 组心脏仅显示弱阳性和可忽略性染色。P 组心脏中 AMPK 磷酸化显著增加。
在接受长时间机械通气的兔中连续输注大剂量丙泊酚会导致高血脂、肝功能障碍、CK 水平升高、AMPK 激活和心肌损伤。能量需求与利用之间的不平衡可能导致 PRIS。
